CHARISMA revisited: is the glass half full or just empty?

The landmark CHARISMA study attempted to show that combination therapy with aspirin plus clopidogrel was superior to aspirin alone in a mixed population of patients with known vascular disease or those with risk factors for vascular disease. Although the study was negative for the combined group, a re-analysis of the outcomes and event rates showed striking differences between the two major patient types. Whereas individuals with risk factors only did not benefit from combination therapy, those with symptomatic vascular disease had a statistically significant 12% relative risk reduction in stroke/MI/vascular death with combination therapy vs aspirin alone. This dichotomous result was due largely to different event rates for the aspirin monotherapy group, being much higher in the symptomatic population compared to the risk factor group. Severe bleeding was not increased significantly for the symptomatic patients taking combination therapy vs aspirin alone. Based on these analyses, it may be premature to abandon combination therapy in a high-risk symptomatic population, especially since aspirin alone appears to have a high failure rate.